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WO2018197451A1 - Activateur de neutrons entraîné par accélérateur destiné à une curiethérapie - Google Patents

Activateur de neutrons entraîné par accélérateur destiné à une curiethérapie Download PDF

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Publication number
WO2018197451A1
WO2018197451A1 PCT/EP2018/060416 EP2018060416W WO2018197451A1 WO 2018197451 A1 WO2018197451 A1 WO 2018197451A1 EP 2018060416 W EP2018060416 W EP 2018060416W WO 2018197451 A1 WO2018197451 A1 WO 2018197451A1
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WO
WIPO (PCT)
Prior art keywords
neutron
target
activation
mev
reflector
Prior art date
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Ceased
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PCT/EP2018/060416
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English (en)
Inventor
Luca MACIOCCO
Stefano Buono
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Advanced Accelerator Applications SA
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Advanced Accelerator Applications SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US16/605,543 priority Critical patent/US11257603B2/en
Priority to ES18718471T priority patent/ES2922003T3/es
Priority to EP18718471.8A priority patent/EP3615142B1/fr
Priority to JP2020508080A priority patent/JP7111802B2/ja
Priority to EP22160129.7A priority patent/EP4029565A1/fr
Priority to CN202210475158.9A priority patent/CN114887240A/zh
Priority to CN201880027293.9A priority patent/CN110831663B/zh
Application filed by Advanced Accelerator Applications SA filed Critical Advanced Accelerator Applications SA
Priority to PL18718471.8T priority patent/PL3615142T3/pl
Publication of WO2018197451A1 publication Critical patent/WO2018197451A1/fr
Anticipated expiration legal-status Critical
Priority to US17/582,345 priority patent/US20220148753A1/en
Priority to JP2022116632A priority patent/JP7427724B2/ja
Priority to US18/210,133 priority patent/US20230326621A1/en
Priority to US18/915,271 priority patent/US20250037895A1/en
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/04—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators
    • G21G1/06—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators by neutron irradiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N2005/1085—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy characterised by the type of particles applied to the patient
    • A61N2005/1091—Kilovoltage or orthovoltage range photons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/001—Recovery of specific isotopes from irradiated targets
    • G21G2001/0094—Other isotopes not provided for in the groups listed above
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21K—TECHNIQUES FOR HANDLING PARTICLES OR IONISING RADIATION NOT OTHERWISE PROVIDED FOR; IRRADIATION DEVICES; GAMMA RAY OR X-RAY MICROSCOPES
    • G21K1/00—Arrangements for handling particles or ionising radiation, e.g. focusing or moderating
    • G21K1/06—Arrangements for handling particles or ionising radiation, e.g. focusing or moderating using diffraction, refraction or reflection, e.g. monochromators
    • H—ELECTRICITY
    • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
    • H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
    • H05H3/00—Production or acceleration of neutral particle beams, e.g. molecular or atomic beams
    • H05H3/06—Generating neutron beams

Definitions

  • the field of the invention is that of activation of doses of injectable suspensions of particles through the production of a suitable neutron field.
  • the invention particularly relates to a neutron activator for production of radioisotopes of interest, which operating principle is based on the interaction of a proton beam with a solid target, which generates neutrons that are then moderated/reflected in a solid assembly to obtain a favourable neutron spectrum for the (n, ⁇ ) reactions in the isotopes of interest (for example 165 Ho, and 176 Lu).
  • Treatment of cancer tumours is based on three main therapeutic classes (frequently combined for increasing the chances of recovery): surgery, chemotherapy and external radiotherapy.
  • Brachytherapy or "in situ” radiotherapy is often recommended in addition to surgery or chemotherapy (as in breast or cervical tumors), or in alternative, constituting then the exclusive first-line treatment (as in prostate cancer in US, treatment of hepatocarcinomas, or other hepatic tumors).
  • Rapidly dividing cells are particularly sensitive to damage by radiation. For this reason, some cancerous growths can be controlled or eliminated by administering or planting a small radiation source, usually a gamma or beta emitter, in the target area.
  • a small radiation source usually a gamma or beta emitter
  • brachytherapy procedures it that they give less overall radiation to the body, minimising the exposure of healthy tissues, are more localized to the target tumor and are cost-effective.
  • ⁇ -emitting radioisotopes can be produced through neutron irradiation of the corresponding stable isotopes.
  • One of the objects of the present disclosure is to propose an alternative to the production of radioisotopes for medical use, in nuclear reactors.
  • Another object is to improve the efficiency of the method of production of radioisotopes for medical use.
  • Another object of the invention is to provide a device and a method for neutron activation of a material, for producing radioisotopes.
  • WO 98/59347 discloses that a material exposed to a neutron flux by distributing it in a neutron-diffusing medium surrounding a neutron source can be used to produce useful radio-isotopes, in particular for medical applications, from the transmutation of readily- available isotopes included in the exposed material.
  • the neutron source consists of a beryllium or lithium target bombarded with a charged particle beam.
  • WO 2016/037656 discloses a method and an activator that enhances captures in the resonance region. The strength of the flux of neutrons is optimized by reflectors and /or moderators.
  • WO 98/59347 proposes some general approaches aiming at reducing the activator size while exploiting the neutron-elastic-scattering properties of lead, and therefore the Adiabatic Resonance Crossing principle in the activation area.
  • This approach has been numerically and experimentally analysed in 2005-2009 by the inventors with the experimental validation of an activator with a lead core and a graphite reflector.
  • the results of such research led to the conclusion that the most efficient approach to activate the considered isotopes was not to use the peculiar properties of lead (transparency and elastic scattering) but focusing on an efficient moderation-reflection, which provides the solution of the present invention.
  • the optimal position of the samples is as close as possible to the proton target rather than in specific positions in the so-called Diffuser.
  • WO 2016/022848 discloses neutron source comprising a spherical metallic target and a spherical reflector-moderator surrounding the target, the target and the reflector-moderator being immersed in a medium containing the material to activate.
  • the material With the neutron source of WO 2016/022848, the material is randomly activated which increases the time for activating the material and prevents large amounts of activated material to be obtained. In addition, recovery of the activated material is complex and not adapted to radioisotopes suitable for nuclear medicine therapy with short half-lives as the case for the present invention.
  • the neutron activator configuration, especially the reflector position of WO 2016/022848 will not allow favorable activation yield for radioisotopes other than Mo-99, as produced by the following neutron capture reaction ⁇ -98( ⁇ , ⁇ ) ⁇ - 99.
  • the size of the reflector and potential based material implies industrial and maintenance complexity as well as preventing from a compact process.
  • Another object of the disclosure is therefore to provide an improved system compared to the activator disclosed in WO 98/59347, WO 2016/037656 and WO 2016/022848.
  • the neutron activator for neutron activation of a material, the neutron activator being configured to produce neutrons from an interaction with a proton beam emitted along a beam axis, the proton beam having an energy comprised between 16 MeV and 100 MeV, preferably 30 MeV and 70 MeV and a beam intensity up to 1 niA, preferably up to 350 ⁇ for 70 MeV and up to 1 mA for 30 MeV, the neutron activator comprising: - a neutron source comprising a metallic target presenting a longitudinal axis intended to be arranged parallel, and especially coaxial, to the beam axis, and
  • Beryllium reflector-moderator peripheral to the neutron source and comprising a neutron activation area configured to accommodate the neutron source and the material to be activated, the neutron activation area of the Beryllium reflector-moderator comprising a bore extending along a bore axis and configured to accommodate the neutron source so that the bore axis and the longitudinal axis are coaxial.
  • the neutron activation area of the Beryllium reflector-moderator may further include at least one activation channel extending along a channel axis parallel to the bore axis at the vicinity of the bore, the activation channel being configured to load the material to be activated.
  • the neutron activation area may comprise a plurality of activation channels distributed, especially equally distributed, around the bore.
  • the metallic target may have a hollow conical shape, the longitudinal axis of said conical target being aligned with the proton beam and the neutron activator further comprises a cooling area in direct contact with the outer surface of the target for receiving a flow of fluid for cooling the target during neutron generation.
  • Said cooling fluid may be a liquid, for example water.
  • the aperture of the conical target and the thickness of its lateral walls may be optimized so that
  • the power density inside the target is reduced to at least 50% as compared to the power density in a target where all the protons received from the proton beam release their thermal energy inside the target, and (iii) the number of generated neutrons in the target is at least 70% equal to the number of generated neutrons in a target having a thickness where all the protons received from the proton beam release their thermal energy inside the target.
  • the aperture of the conical target and the thickness of its lateral walls may be optimized so that
  • the aperture of the hollow conical target is comprised between 20° and 45°.
  • the neutron activator may further comprise, housed in the reflector-moderator:
  • a flow guide delimiting the cooling area for guiding the cooling fluid along the outer surface of the target and obtain the desired velocity as a flow from the inlet channel to the outlet channel
  • the above-defined flow guide is at least partly conical so that said conical flow guide covers the outer surface of the conical target thereby delimiting a cooling area surrounding the outer surface of the target.
  • the metallic target is made of Beryllium or Tantalum.
  • the Beryllium reflector-moderator is cylindrical along the bore axis.
  • the neutron activator may present an overall dimension that does not exceed the volume of a cube of 1 meter side, preferably 0.75 meter side, and for example 0.50 meter side.
  • the neutron activator may further comprise a second reflector-moderator embedding said Beryllium reflector-moderator.
  • the invention also relates to a neutron activation system for neutron activation of a material, comprising:
  • a generator configured to produce a proton beam along a beam axis, the proton beam having an energy comprised between 16 MeV and 100 MeV, preferably 30 MeV and 70 MeV and a beam intensity up to 1 niA, preferably up to 350 ⁇ for 70 MeV and up to 1 mA for 30 MeV,
  • the neutron activation system may further comprises a supplying device for loading the material to be activated, the supplying device being connected to the activation channel and configured to move samples of material to be activated along the activation channel.
  • the present invention also relates to the use of the neutron activator as previously described, for producing radioisotopes, preferably radiopharmaceuticals.
  • said radioisotope is a ⁇ " emitting radioisotope suitable for Nuclear Medicine applications, preferably 166 Ho, 186 Re, 188 Re, 177 Lu, 198 Au, 90 Y, 227 Ra and 161 Tb.
  • Another object of the present invention is a method for neutron activation of a material, said method comprising:
  • the target is cooled by a flow of cooling liquid, preferably water, at a static pressure comprised between 1 and 20 Bar and reaching, near the target surface, speeds comprised between 8 and 15 m/s.
  • said material to be activated is contained within or in the form of a microparticle or nanoparticle, for example of Holmium-oxide micro/nanoparticles.
  • the micro/nanoparticles are in a liquid suspension.
  • said material is contained in a capsule, and said capsule is placed at the activation area by moving the capsule within an activation channel embedded in the reflector-moderator.
  • FIG. 1 is a schematic illustration of the neutron activator according to the present disclosure
  • FIG. 2 is a schematic illustration of a cylinder- shaped target assembly including the hollow conical target and its cooling system
  • FIG. 3 is a schematic illustration of the method for neutron activation using a neutron activator according to the present disclosure
  • FIG. 5 is a graph presenting the cross-sections for the 165 ⁇ ( ⁇ , ⁇ ) 166 ⁇ and the 176 Lu(n,y) 177 Lu transmutations
  • FIG. 6 is a graph presenting the neutron spectra with various moderators.
  • the present disclosure relates to a neutron activator for neutron activation of a material comprising:
  • a neutron source comprising a metallic target suitable for receiving a proton beam of energy comprised between 16 and 100 MeV, preferably between 30 and 70 MeV, and capable of sustaining beam intensities up to 1 mA, preferably up to 350 ⁇ for 70MeV and up to 1 mA for 30MeV and
  • Beryllium first reflector-moderator peripheral to the neutron source and comprising a neutron activation area, - optionally, a second reflector-moderator embedding said Beryllium reflector-moderator.
  • the neutron activator according to the invention advantageously provides an optimized flux of neutrons having the energy of interest in the localized area around the samples to be activated, while remaining sufficiently compact for its use with small-medium sized cyclotrons.
  • a neutron activator of the present disclosure may comprise:
  • a cooling system including a flow guide and a cooling container for guiding a cooling fluid along the outer surface of the conical target
  • the neutron activator may comprise, housed in the reflector-moderator:
  • a flow guide delimiting the cooling area, for guiding the cooling fluid along the outer surface of the target, as a flow from an inlet channel to an outlet channel,
  • the target as neutron source is a hollow conical metallic target which longitudinal axis is aligned with the beam axis of the proton beam.
  • the cooling system includes (i) a cooling container delimiting an inlet channel and an outlet channel for circulation of the cooling fluid, and (ii) a flow-guide delimiting the cooling area for guiding the cooling fluid along the outer surface of the hollow conical metallic target, as a flow from the inlet channel to the outlet channel.
  • the metallic target as neutron source is made of a metallic target presenting a longitudinal axis intended to be arranged parallel to the beam axis of the proton beam for receiving the proton beam which is advantageously generated by a cyclotron.
  • the longitudinal axis and the beam axis are coaxial, namely superposed.
  • the longitudinal axis and the beam axis could be parallel and spaced apart from each other.
  • the target body should be capable of sustaining proton beam of low energy and high intensity, for example, a proton beam energy comprised between 16 and 100 MeV, preferably between 30 and 70 MeV and beam intensities up to 1 niA, preferably up to 350 ⁇ for 70MeV and up to 1 mA for 30MeV.
  • a proton beam energy comprised between 16 and 100 MeV, preferably between 30 and 70 MeV and beam intensities up to 1 niA, preferably up to 350 ⁇ for 70MeV and up to 1 mA for 30MeV.
  • Embodiment with conical target body The target body preferably has a hollow conical shape.
  • the conical shape of the target when aligned with the proton beam enables to optimize the yield of neutrons reaching the activation area surrounding the target.
  • a conical shape of the target with a small aperture angle advantageously increases the interaction surface between the proton beam and the inner surface of the target, thereby lowering the power density in the target while increasing the surface for thermal cooling.
  • the term "conical shape” is used with his broad meaning and refer to cones of circular or non-circular bases (for example the base could be of polygonal or elliptic or any other shape).
  • the conical shape is a right circular cone.
  • the term "hollow" conical shape means that the target is open at its base and essentially consists of the lateral walls of the cone.
  • the longitudinal axis of said hollow conical target is aligned with the proton beam generated by a cyclotron. Accordingly, the proton beam reaches the hollow conical target from the inner surface of the lateral walls of the conical target.
  • the neutron activator advantageously further comprises a cooling area in direct contact with the outer surface of the conical target for receiving a flow of fluid for cooling the target during neutron generation.
  • the final dimensions of the hollow conical metallic target and the cooling area will be adapted with the aim of optimizing the generation of neutrons.
  • the aperture of the conical target and the thickness of its lateral walls are preferably optimized so that part of the protons received from the proton beam have sufficient energy to release the fraction of the thermal energy corresponding to the Bragg peak outside the target in the cooling area, where this heat is easily removed by the cooling flow. This allows to significantly reduce the power density in the solid target, and so improve the target thermal conditions, without significantly reducing the neutron generation
  • At least 50% of the energy coming from the interacting protons is lost outside the target as compared to the energy deposited inside the target if this one would have a thickness where all the protons received from the proton beam release their thermal energy inside it.
  • the aperture and thickness of the conical target are optimized so that the power density is preferably reduced to at least 50%> as compared to the power density in a conical target with aperture and thickness where all the protons would release their thermal energy inside the target.
  • the aperture and thickness of the conical target will be determined so that the number of generated neutrons in the target is at least 70% equal to the number of generated neutrons in a target where all the protons received from a proton beam would release their thermal energy inside the target.
  • the skilled person will be able to determine the above optimized ranges for thickness and aperture of the target, using any appropriate simulation software, and thereby reaching optimized yield for neutron activation using a compact neutron activator.
  • the target has a right circular conical shape and is of Beryllium metal and the energy of the proton beam is between 65 and 75, for example 70MeV, with an intensity between 0.30 and 0.40 mA, typically 0.35mA
  • the thickness of the lateral walls is preferably between 4 and 4.6 mm, for example 3.6mm
  • the aperture of the conical target is preferably between 18 and 22°, for example 20°.
  • the circular base of the target may be set between 27 and 33, for example 30 mm, in order to be adapted to typical beam-line size of 70 MeV cyclotrons.
  • the aperture of the conical target and the thickness of its lateral walls are optimized so that
  • the stresses generated by the temperature gradients in the target remain within the elastic limit of the metallic target.
  • This embodiment may be appropriate when the proton beam characteristics (in terms of energy, intensity and width/current distribution) do not result in very high power densities in the solid target, as for example in the case of a 30 MeV- 185 ⁇ -30 mm beam on a water-cooled conical Beryllium or 30 MeV- 140 ⁇ -30 mm beam on a water-cooled conical Tantalum target.
  • a liquid such as water
  • the metallic target should be made of a material which thickness and composition allow an efficient neutron production, combined with good thermo-mechanical properties.
  • Appropriate material includes without limitation Beryllium, Tantalum, Tungsten and its alloys (e.g. Tungsten-Rhenium or Tungsten-Copper).
  • the metallic target may be made of Beryllium.
  • the metallic target is made of Tantalum.
  • the redox phenomenon typical of Tantalum at temperatures higher that 100°C can be avoided by exposure of the inner surface of the lateral walls of the conical target to a vacuum atmosphere at a pressure of 10 ⁇ 3 mbar or lower (small oxygen concentration), while the temperature of the outer surface in contact with water as cooling fluid is kept below 200°C by the cooling effect of the water itself.
  • a preferred embodiment of the hollow conical target and its cooling system is illustrated in Figure 2.
  • the cooling system comprises
  • the flow guide is in close proximity to the outer surface of the conical target and thereby delimits a cooling area for guiding the cooling fluid all along the outer surface of the conical target.
  • the flow guide is connected to the cooling container which includes:
  • the flow guide is at least partly conical, preferably with similar shape to the conical shape of the target, so that said conical flow guide covers the outer surface of the conical target thereby delimiting a cooling area surrounding the outer surface of the target, sized in order to obtain along the target walls an optimized velocity distribution of the cooling liquid.
  • the assembly of the hollow conical target with the flow guide and the cooling container is cylinder-shaped so that it can be readily housed in the reflector- moderator surrounding said target assembly.
  • thermocouples may be placed on or inserted at the outer surface of the target, for example at the base of the cone, for monitoring the thermal status of the target.
  • the neutron activator according to the present disclosure further includes a reflector- moderator which is peripheral to the neutron source and therefore, surrounds the target and its cooling system.
  • the reflector-moderator further comprises the neutron activation area. Its function is to concentrate the activated neutrons in the area containing the activation samples (activation area) while efficiently slowing-down (moderating) the neutrons down to energies suitable for the activation of the selected isotopes.
  • the reflector-moderator is made of Beryllium or contains at least 90% of Beryllium metal. As shown in the example, the use of Beryllium as material for the reflector- moderator presents different advantages compared with other materials:
  • the first reflector-moderator is hence configured to accommodate the neutron source and the material to be activated.
  • the neutron activation area of the first reflector-moderator comprises a bore extending along a bore axis and configured to accommodate the neutron source so that the bore axis and the longitudinal axis are coaxial.
  • the reflector-moderator surrounds a cylinder-shaped assembly of a hollow conical target and its cooling system (target assembly), said target assembly including
  • the reflector-moderator is cylindrical of circular cross- section, along the bore axis.
  • the reflector-moderator may be cylindrical along the bore axis of any suitable other cross-section.
  • the dimensions of the reflector-moderator are set as to maximize the activation yield of the isotopes while keeping it as small as possible.
  • the activator including the neutron source, the reflector-moderator, optionally together with the second reflector- moderator has an overall dimension that does not exceed the volume of a cube of 1 meter side, preferably 0.75 meter side, and for example 0.50 meter side.
  • the reflector-moderator further includes activation channels for loading the material to be activated at the neutron activation area.
  • the activation channels should enable the loading and unloading of the material to be activated. Said channels may be machined within the reflector-moderator. The skilled person will know how to determine the positions of said activation channels with respect to the target using appropriate simulations, in order to optimize the activation of the radioisotopes.
  • a plurality of activation channels may be disposed on concentric rings around the target.
  • the activation area of the first refiector-moderator also comprises several activation channels extending along a channel axis parallel to the bore axis at the vicinity of the bore.
  • the activation area comprises activation channels distributed around the bore.
  • the activation channels are equally distributed around the bore. For example, in the represented embodiment, a first series of activation channels are evenly distributed around the bore at a first distance from the bore axis and a second series of activation channels are evenly distributed around the bore at a second distance from the bore axis, greater than the first distance.
  • the neutron activator further includes a remote material loading system, for allowing the remote loading-unloading of the material to be activated within the activation channels.
  • the provisions as to the Beryllium reflector-moderator could be provided independently of the provisions regarding the shape of the target.
  • the second reflector-moderator embedding the Beryllium reflector-moderator aims at further slowing down and scattering back the neutrons, already partially moderated, escaping the Beryllium reflector-moderator. Its main purpose is to optimize the activator performances while minimizing the volume, and therefore the cost, of the very expensive Beryllium reflector-moderator.
  • the second reflector-moderator may be made of polyethylene, typically high- density polyethylene.
  • the dimensions of the moderator will be such that the assembled activator, including the target, its cooling system, the reflector-moderator and the second reflector-moderator does not exceed a volume of a cube of 1 meter side, preferably 0.75 meter side, and for example 0.50 meter side.
  • the activator according to the invention is dedicated to neutron activation of particles.
  • Another object of the present invention is to provide a method for neutron activation of a material, said method comprising:
  • said material to be activated is contained within or in the form of a micro or nanoparticles, for example of Holmium-oxide micro or nanoparticles.
  • Holmium-oxide particles are described in "New modality of curietherapy with holmium oxide submicronic particles.” EANM 2009, Annual Congress of the European Association of Nuclear Medicine, October 10-14, 2009, Barcelona, Spain
  • the microparticles or nanoparticles are in a liquid suspension.
  • said material may be contained in a capsule, and said capsule is placed at the activation area by moving the capsule within the activation channels embedded in the reflector-moderator.
  • Figure 3 represents an embodiment of a neutron activation system comprising:
  • a generator such as a cyclotron 13, configured to produce a proton beam along a beam axis, the proton beam having an energy comprised between 16 MeV and 100 MeV, preferably 30 MeV and 70 MeV and a beam intensity up to 1 niA, preferably up to 350 ⁇ for 70 MeV and up to 1 mA for 30 MeV,
  • a neutron activator arranged so that the longitudinal axis of the target is parallel, especially coaxial, to the beam axis, to produce neutrons from the interaction with the proton beam and to activate the material to be activated, and
  • supplying device for loading one or more samples of material to be activated.
  • the method according to the invention is disclosed in relation with the neutron activation system of Figure 3 which represents the different steps of the neutron activation.
  • Samples of material to be activated such as microparticles containing stable targeted isotopes are provided in the form of suitable capsules (15).
  • the capsules are then loaded in the activation channels (5) through the supplying device which may include for example a shielded capsule loader (16) and a transfer system (14).
  • the supplying device is connected to the activation channels (5) and configured to move, preferably in an automated manner, samples of material to be activated along the activation channel (5).
  • the method comprises the use of a pneumatic loading and unloading system, allowing the remote loading-unloading of the capsule(s) within the activation channels.
  • the capsules travel back and forth through a compressed air rabbit system allowing the remote loading/unloading of the particles suspension capsules.
  • the pneumatic system allows also the cooling, by means of a flux of air flowing in all activation channels, of the heat generated by the interactions of the neutrons with the capsules and their content during the irradiation.
  • the proton beam is directed to the metallic target (1) and the protons interact with the metallic target (for example made of Be), thereby generating fast (high energy) neutrons (12).
  • the target is cooled in the cooling area, using for example water flowing from an inlet channel to the outer surface of the target (2).
  • the target is cooled by a flow of cooling liquid, preferably water, at a static pressure comprised between 1 and 20 bar and reaching, near the target surface, speeds comprised between 8 and 24 m/s.
  • the cooling aims at avoiding the boiling of the water while limiting erosion effects on the surface of the solid target or relevant vibration of the target structure.
  • the cooling-water volume has the additional effect of giving a first moderation to the high-energy neutrons flowing out from the target. The relevance of this moderating effect depends on the thickness of the water layer.
  • the water-layer thickness is minimised at the advantage of keeping the activation samples as close as possible to the target and the beryllium reflector as compact as possible.
  • the neutrons are reflected and moderated in the first reflector-moderator (4) for reaching the activation area (10).
  • Neutrons passing through the first reflector-moderator may be further moderated and scattered back by the second reflector-moderator (6).
  • the present invention also relates to the use of the neutron activator as previously described, for producing radioisotopes, preferably for use in radiopharmaceuticals and medical devices.
  • the choice of the radioisotopes depends on three main characteristics: the half-life, the ⁇ " energy and the ⁇ energy (Table 1). Shorter half-life allows shorter permanence period in the treating unit (repeated treatment possible). Higher ⁇ " energy corresponds to higher therapeutic efficiency. Higher ⁇ energy corresponds to better detection with Single photon emission computed tomography (SPECT).
  • SPECT Single photon emission computed tomography
  • said radioisotope is a ⁇ " emitting radioisotope suitable for Nuclear Medicine applications, preferably 166 Ho, 186 Re, 188 Re, 177 Lu, 198 Au, 90 Y, 227 Ra and 161 Tb.
  • Holmium is of particular interest for the application of the present invention as it represents a very good compromise combining a short half- life and high ⁇ " energy, compared with the other radioisotopes.
  • the activator according to the Example is a rectangular parallelepiped with a 50 cm width, 50 cm height, and 56 cm long. It is composed of: - a hollow Beryllium conical target (1),
  • the activation channels (5) are disposed on rings placed in a concentric way around the target.
  • One ring of 16 channels allows a total loading capacity of 64 capsules/doses (4 per channel).
  • Table 2 presents the technical parameters of the activator.
  • Table 2 To limit erosion effects, the cooling water velocity has been limited at around lOm/s, corresponding, with the present dimensions, to a flow rate of about 2 kg/s. With this condition, the maximum temperature of the wall at the interface target/water is expected around 150°C. To avoid boiling, the coolant (water) has to be pressurized at least at 5 bars. Table 3 summarizes the cooling characteristics for the Be target.
  • Be shows very good moderation, yielding significantly higher fluxes in the thermal region with respect to all the other materials, and same level as Pb in the epithermal region.
  • the 166 Ho activation yield is significantly better with the Be reflector-moderator.

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Abstract

L'invention concerne un activateur de neutrons destiné à l'activation de neutrons d'un matériau, l'activateur de neutrons étant configuré pour produire des neutrons à partir d'une interaction avec un faisceau de protons (7), l'activateur de neutrons comprenant : - une source de neutrons comprenant une cible métallique (1), et - un premier réflecteur-modérateur de béryllium (4) périphérique à la source de neutrons et comprenant une zone d'activation de neutrons (10) configurée pour recevoir la source de neutrons et le matériau à activer, la zone d'activation de neutrons (10) du premier réflecteur-modérateur (4) comprenant un alésage configuré pour recevoir la source de neutrons.
PCT/EP2018/060416 2017-04-24 2018-04-24 Activateur de neutrons entraîné par accélérateur destiné à une curiethérapie Ceased WO2018197451A1 (fr)

Priority Applications (12)

Application Number Priority Date Filing Date Title
CN202210475158.9A CN114887240A (zh) 2017-04-24 2018-04-24 用于近距离放射治疗的加速器驱动的中子激活器
ES18718471T ES2922003T3 (es) 2017-04-24 2018-04-24 Activador de neutrones impulsado por acelerador para braquiterapia
EP18718471.8A EP3615142B1 (fr) 2017-04-24 2018-04-24 Activateur de neutrons entraîné par accélérateur destiné à une curiethérapie
JP2020508080A JP7111802B2 (ja) 2017-04-24 2018-04-24 小線源治療のための加速器駆動型中性子放射化装置
EP22160129.7A EP4029565A1 (fr) 2017-04-24 2018-04-24 Activateur de neutrons piloté par accélérateur pour curiethérapie
CN201880027293.9A CN110831663B (zh) 2017-04-24 2018-04-24 用于近距离放射治疗的加速器驱动的中子激活器
PL18718471.8T PL3615142T3 (pl) 2017-04-24 2018-04-24 Napędzany akceleratorem aktywator neutronów do brachyterapii
US16/605,543 US11257603B2 (en) 2017-04-24 2018-04-24 Accelerator-driven neutron activator for brachytherapy
US17/582,345 US20220148753A1 (en) 2017-04-24 2022-01-24 Accelerator-driven neutron activator for brachytherapy
JP2022116632A JP7427724B2 (ja) 2017-04-24 2022-07-21 小線源治療のための加速器駆動型中性子放射化装置
US18/210,133 US20230326621A1 (en) 2017-04-24 2023-06-15 Accelerator-driven neutron activator for brachytherapy
US18/915,271 US20250037895A1 (en) 2017-04-24 2024-10-14 Accelerator-drivenneutron activator for bachytherapy

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EP17305461 2017-04-24

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US17/582,345 Continuation US20220148753A1 (en) 2017-04-24 2022-01-24 Accelerator-driven neutron activator for brachytherapy

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JP (2) JP7111802B2 (fr)
CN (2) CN110831663B (fr)
ES (1) ES2922003T3 (fr)
PL (1) PL3615142T3 (fr)
PT (1) PT3615142T (fr)
WO (1) WO2018197451A1 (fr)

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CN111698822A (zh) * 2020-05-26 2020-09-22 中国原子能科学研究院 一种一体化桌面式中子发生器
CN115151013A (zh) * 2022-08-31 2022-10-04 兰州大学 一种中子俘获照射系统

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ES2961653T3 (es) * 2018-07-09 2024-03-13 Advanced Accelerator Applications Activador de neutrones, sistema de activación de neutrones que comprende dicho activador de neutrones y método para la activación de neutrones que implementa dicho activador de neutrones
WO2020210147A1 (fr) * 2019-04-08 2020-10-15 The Regents Of The University Of California Systèmes et procédés de production d'actinium-225
CN113556858B (zh) * 2021-06-23 2025-02-14 散裂中子源科学中心 一种中子产生靶
CN115715852A (zh) * 2022-11-18 2023-02-28 哈尔滨理工大学 一种基于蒙特卡洛模拟的囊结构优化方法

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CN111698822B (zh) * 2020-05-26 2021-07-16 中国原子能科学研究院 一种直立式中子发生器
CN115151013A (zh) * 2022-08-31 2022-10-04 兰州大学 一种中子俘获照射系统
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US20230326621A1 (en) 2023-10-12
JP2022153511A (ja) 2022-10-12
CN114887240A (zh) 2022-08-12
US20200126683A1 (en) 2020-04-23
JP2020517973A (ja) 2020-06-18
US11257603B2 (en) 2022-02-22
PL3615142T3 (pl) 2022-08-08
JP7427724B2 (ja) 2024-02-05
EP4029565A1 (fr) 2022-07-20
EP3615142B1 (fr) 2022-04-06
PT3615142T (pt) 2022-06-28
US20250037895A1 (en) 2025-01-30
CN110831663B (zh) 2022-05-13
ES2922003T3 (es) 2022-09-06
CN110831663A (zh) 2020-02-21
US20220148753A1 (en) 2022-05-12
JP7111802B2 (ja) 2022-08-02

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